JACC: CARDIOVASCULAR INTERVENTIONS

VOL. 7, NO. 12, 2014

ª 2014 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

ISSN 1936-8798/$36.00

PUBLISHED BY ELSEVIER INC.

http://dx.doi.org/10.1016/j.jcin.2014.05.035

Outcomes After Percutaneous Coronary Intervention With Stents in Patients Treated With Thoracic External Beam Radiation for Cancer Jackson J. Liang, DO,* Terence T. Sio, MD, MS,y Joshua P. Slusser, BS,z Ryan J. Lennon, MS,z Robert C. Miller, MD,y Gurpreet Sandhu, MD,x Abhiram Prasad, MDk

ABSTRACT OBJECTIVES The aim of this study was to assess outcomes after percutaneous coronary intervention (PCI) with stents in patients treated with thoracic external beam radiation therapy (EBRT). BACKGROUND Thoracic EBRT for cancer is associated with long-term cardiotoxic sequelae. The impact of EBRT on patients requiring coronary stents is unclear. METHODS We analyzed outcomes after PCI in cancer survivors treated with curative thoracic EBRT before and after stenting between 1998 and 2012. Reference groups were propensity-matched cohorts with stenting but no EBRT. Primary endpoint was target lesion revascularization (TLR), a clinical surrogate for restenosis. Secondary endpoints included myocardial infarction (MI) and cardiac and overall mortality. RESULTS We identified 115 patients treated with EBRT a median 3.6 years after stenting (group A) and 45 patients treated with EBRT a median 2.2 years before stenting (group B). Long-term mean TLR rates in group A (3.2 vs. 6.6%; hazard ratio: 0.6; 95% confidence interval: 0.2 to 1.6; p ¼ 0.31) and group B (9.2 vs. 9.7%; hazard ratio: 1.2; 95% confidence interval: 0.4 to 3.4; p ¼ 0.79) were similar to rates in corresponding control patients (group A: 1,390 control patients; group B: 439 control patients). Three years post-PCI, group A had higher overall mortality (48.6% vs. 13.9%; p < 0.001) but not MI (4.8% vs. 4.3%; p ¼ 0.93) or cardiac mortality (2.3% vs. 3.6%; p ¼ 0.66) rates versus control patients. There were no significant differences in MI, cardiac, or overall mortality rates in group B. CONCLUSIONS Thoracic EBRT is not associated with increased stent failure rates when used before or after PCI. A history of PCI should not preclude the use of curative thoracic EBRT in cancer patients or vice versa. Optimal treatment of cancer should be the goal. (J Am Coll Cardiol Intv 2014;7:1412–20) © 2014 by the American College of Cardiology Foundation.

A

s the prevalence and survival of both coro-

it results in a substantial amount of cardiac exposure.

nary

cancer

The adverse cardiovascular impact of thoracic EBRT

continue to increase among the aging popu-

is well established and includes coronary atheroscle-

lation, the 2 diseases often coexist in the same indi-

rosis, restrictive cardiomyopathy, constrictive peri-

vidual. External beam radiation therapy (EBRT) is a

carditis, and valvular heart disease. Percutaneous

cornerstone of cancer therapy; however, when used

coronary intervention (PCI) using stents, performed

for certain thoracic malignancies (e.g., breast, lung,

in the vast majority, has become the predominant

Hodgkin and non-Hodgkin lymphoma, esophagus),

mode of revascularization. Thus, in many patients

artery

disease

(CAD)

and

From the *Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota; yDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota; zDepartment of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota; xDivision of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota; and kCardiovascular Sciences, St. George’s, University of London, London, United Kingdom. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received January 29, 2014; revised manuscript received May 10, 2014, accepted May 22, 2014.

Liang et al.

JACC: CARDIOVASCULAR INTERVENTIONS VOL. 7, NO. 12, 2014 DECEMBER 2014:1412–20

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Radiation Therapy and Coronary Artery Stents

with an initial diagnosis of CAD, cancer develops,

allergy or marked intolerance, lifelong aspirin

ABBREVIATIONS

requiring EBRT. Conversely, many cancer survivors

therapy was recommended.

AND ACRONYMS

RADIATION THERAPY. All patients had a

BMS = bare-metal stent(s)

biopsy-confirmed

CAD = coronary artery disease

who received EBRT subsequently require PCI for symptomatic CAD. Despite the deleterious impact of EBRT on the heart and concerns regarding impaired vascular healing, radiation brachytherapy was used in the past as a treatment for coronary restenosis with bare-metal stents (BMS) (1,2). However, long-term follow-up demonstrated a delayed risk of stent failure (3,4). This observation raises the possibility that EBRT may adversely affect outcomes in patients with coronary stents, but there is a paucity of data on the subject. Thus, the aim of this study was to assess clinical outcomes after PCI with stents in cancer patients treated with EBRT before or after the coronary revascularization.

or

radiographic

(early-

stage non-small cell lung cancer) diagnosis of

DES = drug-eluting stent(s)

malignancy and received EBRT with a cura-

EBRT = external beam

tive intent. The malignancies included can-

radiation therapy

cers of the lung (small cell or non-small cell),

IQR = interquartile range

breast, thymus, gastrointestinal tract (in-

MI = myocardial infarction

cluding the biliary tree, stomach, esophagus,

PCI = percutaneous coronary

and pancreas), and lymphoma. The majority

intervention

of patients had a cancer above the dia-

TLR = target lesion

phragm. The TNM staging was assigned and

revascularization

defined according to the American Joint Committee on Cancer Cancer Staging Manual, Sixth Edition (5). The cancers were staged from I to IVA (stage IVA for esophageal carcinoma is considered locally advanced and potentially curable), with none of the cancers

METHODS

having M1 staging (proven metastasis at initial diagnosis, usually noncurable by combined modalities

STUDY POPULATION. In this retrospective analysis,

including radiation). The non-Hodgkin lymphoma

patients referred to the Mayo Clinic in Rochester,

patients received a dose ranging from 35 to 70 Gy, and

Minnesota, for curative thoracic EBRT for the treat-

the 3 Hodgkin patients received total radiation doses

ment of malignancy between March 1998 and

of 24, 24, and 30.6 Gy, respectively. All EBRT simu-

November 2012 who were also treated with PCI at our

lation plans were performed with computed to-

institution during the same time interval, either

mography imaging. A radiation oncologist (T.T.S.)

before or after EBRT, were included. The EBRT-

reviewed each individual dosimetric plan and verified

treated population was restricted to malignancies

cardiac involvement by EBRT. Fifteen cases of ste-

that would result in significant cardiac exposure.

reotactic body radiation therapy (all for early-stage

These patients were then cross-referenced with the

lung cancers) and 11 cases of intensity-modulated

Mayo Clinic PCI database. The patients were divided

radiotherapy (a more modern radiation technique)

into 2 groups: those who had PCI before EBRT (group

were included.

A) and those who had PCI after EBRT (group B). Two separate control groups of propensity-matched pa-

CARDIAC CLINICAL OUTCOMES. The primary out-

tients who had PCI but no EBRT were identified for

come of this study was target lesion revascularization

comparison. The study was approved by the Mayo

(TLR), a surrogate for clinically significant stent ste-

Clinic’s Institutional Review Board.

nosis and defined as any attempted percutaneous or

PCI PROCEDURE. The Mayo Clinic PCI registry in-

cludes demographic, clinical, angiographic, and procedural data. Immediate and in-hospital events are recorded, and each patient is surveyed by telephone contact by trained research coordinators using a standardized questionnaire at 6 months, 1 year, and then annually after the procedure. All adverse events are confirmed by reviewing the medical records of the patients followed at our institution and by contacting the patients’ physicians and reviewing the hospital

surgical revascularization of the target lesion at any time after the initial procedure. Secondary outcomes included MI, cardiac mortality, and all-cause mortality. MI was diagnosed in the presence of 2 of the following 3 criteria: 1) typical chest pain for at least 20 min; 2) increase in creatine kinase (or the myocardial band fraction) >2 times normal; and 3) a new Q-wave on an electrocardiogram. Deaths were considered cardiac if they were due to MI, sudden death (within 1 h of cardiac symptoms), or other cardiac causes (e.g., congestive heart failure, arrhythmia).

records of patients followed elsewhere. Only patients who had successful PCI with at least

STATISTICAL ANALYSIS. Continuous variables are

1 BMS or drug-eluting stent (DES) were included.

summarized as mean  SD unless otherwise noted;

All patients received dual-antiplatelet therapy for a

discrete variables are summarized as frequency

minimal duration of 1 month for a BMS and 12 months

(percentage). For both groups A and B, a propensity

in those treated with a DES. In the absence of an

score was developed to predict case membership

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Liang et al.

JACC: CARDIOVASCULAR INTERVENTIONS VOL. 7, NO. 12, 2014 DECEMBER 2014:1412–20

Radiation Therapy and Coronary Artery Stents

T A B L E 1 Baseline Demographic and Clinical Characteristics, Presenting Characteristics at the Time of PCI, and Medications

at Hospital Discharge After PCI

Age, yrs Male Body mass index, kg/m2 Lifelong nonsmoker Congestive heart failure

PCI Before EBRT (n ¼ 115)

Control Patients (n ¼ 1,930)

66.1  9.5

66.3  9.5

50 (43) 29.4  5.9

839 (43) 29.5  6.2

EBRT Before PCI (n ¼ 45)

Control Patients (n ¼ 439)

70.2  9.7

70.2  9.6

16 (36)

156 (36)

0.76

29.7  6.8

29.4  5.9

p Value

0.59 *

p Value

0.81 * 0.78

34 (30)

554 (29)

0.96

17 (40)

183 (42)

0.84

6 (5)

67 (4)

0.63

8 (18)

79 (18)

0.95

Diabetes mellitus

25 (22)

349 (18)

9 (20)

106 (24)

0.72

Hypertension

81 (74)

1,209 (65)

0.036

0.27

34 (76)

323 (77)

0.71

Hyperlipidemia

66 (65)

1,187 (68)

0.70

32 (73)

308 (74)

0.97

History of myocardial infarction

20 (18)

307 (16)

0.68

7 (16)

74 (17)

0.86

History of PCI

15 (13)

249 (13)

0.93

6 (13)

44 (10)

0.72

History of coronary artery bypass grafting

10 (9)

154 (8)

0.77

2 (4)

31 (7)

0.47

Peripheral vascular disease

14 (12)

186 (10)

0.34

5 (11)

43 (10)

0.65

History of stroke or TIA

9 (8)

107 (6)

0.33

5 (11)

46 (11)

0.96

Moderate to severe renal disease

3 (3)

51 (3)

0.85

2 (4)

21 (5)

0.82

Characteristics at the time of PCI Pre-procedural shock Unstable angina

2 (2)

58 (3)

0.37

3 (7)

14 (3)

0.79

73 (63)

1,212 (63)

0.98

23 (51)

208 (47)

0.54

60 (52)

995 (52)

19 (42)

196 (45)

Left ventricular ejection fraction, % >40